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1980

2527

A Tautomerisable Macrocyclic Compound containing Two Aza-bridged

2,2- Bipyridine Moieties
By Shojiro Ogawa * and Shinsaku Shiraishi, Institute of Industrial Science, The University of Tokyo, Roppongi,

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Minato- ku, Tokyo,Japan

A novel macrocyclic compound containing two aza-bridged 2,2-bipyridine moieties was prepared by the templated
reaction of 6,6-dichloro-2,2-bipyridine. Spectroscopic investigation shows that the aza-bridging atoms form
an amine @ imine tautomeric system. The tautomerism is dependent upon the solvent; the imine form is
preferred in non- polar solvents such as chloroform and benzene, while the amine form is favoured almost exclusively
in polar solvents such as water, alcohol, acetonitrile, dimethyl sulphoxide, or tetrahydrofuran.

THE chemistry of synthetic aza-macrocycles and their

metal complexes is in a stage of rapid development,l
attempts having been made t o relate their structural
properties and reactivities with those of metalloporphyrins and corrins.
While prot otropic taut omerisat ion of het eroaromatic
amines to the corresponding imines has long been of
interest,2little has been done to develop these compounds

Q(-J
CL

(11

compounds by means of X-ray photoelectron spectroscopy.5 We report here the synthesis of a novel hexaaza-macrocycle by the templated reaction of 6,6dihalogeno-2,2-bipyridine and describe its unusual
tautomeric properties.
The general scheme for the synthesis of the new ligand
involves the template cyclisation of 6,6-dichloro-2,2bipyridine with ammonium tetrachlorozincate, (NH,),ZnCl,, and subsequent demetallation of the resulting
zinc complex.
6,6-Dibromo-Z,2-bipyridine
has previously been prepared by the inconvenient procedure of gas-phase
bromination of 2,2-bi~yridine.~Hence we obtained

CH~CH~CHZCH~

(41

&N

(5)

as macrocyclic agents. An interest in the tautomeric

properties of diquinolylamines 3 has led us to synthesise
a series of new macrocyclic compounds containing
pyridine rings which may show potent tautomeric
behaviour in various environments. We have recently
reported the syntheses of conjugated macrocycles by
thermal dimerisation of 1 ,lo-phenanthroline derivatives:
and have studied the electronic structures of these

6,6-dichloro-2,2-bipyridine(1) by the reaction of 1,ldimethyl-2,2-bipyridine-6,6(1HJ1H)-dione

7 with PCl,
in POC1,. Fusion of 1 equiv. of (1) with 7 equiv. of
(NH,),ZnCl,, which was obtained by heating ZnC1, and
NH,Cl in water,* afforded the zinc complex (2), m.p.
470 C (decornp.) in 68% y.ield. Direct evidence for
a metal-bound macrocycle is provided by the mass
spectrum. The largest m/e values (400, 402, and 404)
correspond to the complex of
66Zn, and 68Zn,
respectively, with abundance ratios consistent with the
isotopic abundance of zinc. 6,6-Diamino-2,2-bipyridine (3) was also formed in 6% yield.
The zinc complex is quite stable in mineral acids,
even in hot trifluoroacetic acid. Bubbling of dry
hydrogen chloride through its solution in sulphuric acid
barely gave the metal-free macrocycle (4) (50%, m.p.
460 C decornp.). The molecular weight of (4) was
confirmed by the high-resolution mass spectrum. The
i.r. spectrum exhibited no absorption in the normal N-H

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2528

J.C.S. Perkin I

stretching region, but a broad absorption at 2 8003 000 cm-l indicated the formation of an intramolecular
N-H
N interaction, and thus supported the structure
(5) rather than (4). In solution, however, it shows
remarkable colour change with the solvent used. A
solution in a non-polar solvent such as chloroform and
benzene is deep yellow in colour, while that in water,
alcohol, acetonitrile, dimethyl sulphoxide, or other
polar solvents is almost colourless. In chloroform, the
fully conjugated imine form is thought to predominate,
and leads to absorption of light in the visible region,
whereas in acetonitrile or other polar solvents the partially conjugated amine form is the major form. As a
model compound of (4),di-n-butyl macrocycle (6) was
prepared from (4)by treatment with sodium hydride
and then with n-butyl iodide in dioxan. The l H n.m.r.
spectrum shows that the two n-butyl groups are situated
on nitrogen bridges as in (6), because the protons of the
pyridine rings give rise to only three signals. The
spectrum of this compound shows only small solvent
dependence.
The electronic spectra of the macrocycle and model
compounds are shown in Figure 1. The spectrum of the

I 1

M e SMe
II
0

aJ
V
c
U

n
Q

400

300

500

600

hinm
FIGURE
2 Spectral change of the macrocyclc by addition of
dimethyl sulphoxide in CHCI,; [Macrocycle] = 2.80 x lov5
mol l-l, [DMSO] = 0 (l),0.07 ( 2 ) , 0.17 (3), 0.34 (4),0.67 ( 5 ) ,
and 0.98 (6) mol 1-I in CHCI,. Arrows indicate the direction
of the absorbance changes for increasing DMSO concentration

in Figure 2, which refers to measurements in chloroformdimethyl sulphoxide. Isosbestic points were observed
at 310 and 405 nm. Figure 3 shows relative absorbances
a t 340 nm in various solvent systems. It is interesting

3
ul
0
d

3.5-

1.0

Q
U

Zi 0.9

T
3.0

3 00

LOO

500

0-8

600
U

h /nm
?
FIGURE
1 Electronic spectra of the hexa-aza-macrocycle in
0.7
CHC1, (------)
and in MeCN (- -), the zinc hexaaza-macrocycle in dimethyl sulphoxide (- - - -) , and the ar
>
di-n-butyl hexa-aza-macrocycle in CHCl, (- - - - -1
Z 0.6

macrocycle in acetonitrile is very similar to that of the 4

dibutyl macrocycle (6), whereas the spectrum in chloro- cc
0.5 form is similar t o that of the zinc complex (2) whose
electronic structure may resemble that of (5). This
fact indicates that the equilibrium is shifted in favour
0.4of the amine tautomer (4)in acetonitrile, whereas the
O
0.2
0.4
0.6
0.8
,1.0
1.2
1-4
imine form (5) is favoured almost exclusively in chloroc / m o \ t-
The change in the structure with
may be FIGURE
J

Variation of relative absorbance caused by addition

described in terms of inter- and intra-molecular hydrogen
of polar solvelit to sojutions of tile hcxa-aza-n1acrocyclc diss&ed in chloroform (2.80 x 10-5 mol l-l), with A, being abbonding. Thus, as solvent polarity is varied in a
sorbance a t zero-added polar solvent. Curve 1, ether; curve
mixture of solvents, the absorption mOveScontinuously
2, dimethyl sulphcxide; curve 3, acetonitrile; curvc 4, tctrawith clean isosbestic points. Typical spectra are shown
hydrofuran; curve 5, methyl ethyl ketone
I

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1980
t o note that di-(2-pyridyl)amine exists exclusively in
the amine form,g and that the macrocycle prepared by
dimerisation of 2,9-diamino-l, 10-phenantliroline contains two hydrogen atoms within the macrocycle.*
The lH n.rn.r. spectrum of (4) could not be determined
in a neutral organic solvent owing to its limited solubility, but the spectrum in trifiuoroacetic acid was
obtained and showed two separate signals due to
hydrogen atoms attached to tlie two kind of nitrogen
atom; one is due t o the inner NH protons which is
abnormally deshielded (8 17.2) and tlie other (at 6 10.2)
is due to the outer NH protons. This indicated that
the compound is present as a dication (7a) or (7b) in the
solution. A paramagnetic ring current owing to a 4 ~
electron system of the macrocycle as well as the very
strong hydrogen bonding within the ring seems to be the
reason for the abnormal clcshieldiiig o the inner NH
protons.
H.

(7al

(7b)

EXPERIMENTAL

1.r. spectra were measured for KBr discs with a JASCO

IRA-2 spectrophotometer. N.m.r. spectra were determined with Hitachi R-20A (60 MHz) and R-22 (90 MHz)
instruments with tetramethylsilane as internal reference.
Mass spectra were obtained by direct insertion into the ion
source of a Hitachi RMU-7M instrument. Electronic
spectra were measured with a JASCO UVIDEC-505
spectrophotometer a t 25 C.
l,l-Di~netltyZ-2,2-bipyridine-6,G(l H , 1H)-dione.-A mixture of 2,2-bipyridine (20 g) and dimethyl sulphate (70 ml)
was niaiiitained a t 100 C for 1 h. After cooling, dry
ether (200 nil) was added to the reaction mass with stirring.
The hygroscopic white precipitate was used without further
purification. To an ice-cooled solution of potassium
ferricyanide (120 g) in water (400 ml) were added alterna tely in small portions a solution of sodium hydroxide
(150 g) in water (500 ml) and a solution of the foregoing
white solid in water (500 ml), whilst maintaining the
temperature under 5 C. The mixture was then adjusted
to pH 8-9
by dropwise addition of concentrated hydrochloric acid solution with cooling and extracted with
chloroform. After drying (Na,SO,), the solvent was
evaporated off to afford a white solid which was recrystallisetl from benzene to give the diketone (18 g, 65%), m.p.
210-211 C, v,,,:~~. (KBr) 1650 cm-l ( G O ) ; S(CDC1,) 3.29
( G H, s, NCH,), 6.19 (2 H, dd, J 6.6 and 1.2 Hz), 6.67 ( 2 H,
dtl, J 9.0 and 1.2 Hz), and 7.39 (2 H, dd, J 9.0 and 6.6
HZ).
~,R-nicllloro-2,2-bipyr~dine (1) .-The
diketone (7.0 g),
phosphorus pentachloride ( 15 g) , and phosphoryl chloride
(1.10 nil) were reflusecl for 20 11. After removal of the

excess of phosphoryl chloride by distillation under reduced

pressure, ice-water was added and the solution basified
with ammonia. The precipitate crystallised from benzene
as needZes (7.2 g, 99%), m.p. 218-219 C (Found: C, 53.5;
H, 2.8; N, 12.4. CloH,Cl,Nz requires C, 53.4; H, 2.7; N,
12.4%); G(CDC1,) 7.28 (d, 5-H), 7.70 (t, 4-H), and 8.29
((1, 3-H).
Zinc Hexa-aza-macrocycle (2).--The dichloride (1) (2.0 g)
and ammonium tetrachlorozincate ( 15 g) were mixed
thoroughly in a mortar and heated under nitrogen a t 320330 C for 6 h. Removal of the sublimed unchanged
starting inaterial (0.43 g, 22%), washing with water,
treatment with 10% sodium hydroxide (100 ml), and further
washing with water afforded a greenish yellow solid (1.8 g).
-The solid was heated in a sublimation apparatus at 200 C
and 0.5 mmHg for 3 h to give 6,6-diamino-2,2-bipyridine
(3) as a sublimate (100 mg, 6%), m.p. 186 C (lit.,, 185 C).
The residue was redissolved in aqueous 5% acetic acid and
was reprecipitated with sodium hydroxide to give the zinc
hexa-aza-).nacrozycle (2) (1.2 g, 68%), which crystallisecl
from a small amount of acetic acid as fine yellow needles,
1n.p. 470 C (decomp.) (Found: C, 59.8; H, 3.5; N, 20.5.
C,,H,,N6Zn requires C, 59.8; H, 3.0; N, 20.5%); nz/e
400, 402, and 404.
3,lO-Dihydrotetrupyrid~[Z,
1,6-de:2,1,6-gh:2, l,fikl:2, 1,6-na][1,3,5,8,10,12]hexa-~zacycZotetradeGine
(4).
-A stream of dry hydrogen chloride was passed through
a solution of the zinc hexa-aza-macrocycle (2) (760 mg)
in concentrated HzS04(30 ml) for 6 h, after which it was
filtered on to ice and basified with aqueous ammonia. The
precipitate was washed with dilute aqueous ammonia,
and extracted with water. Recrystallisation from water
afforded orange needles (320 mg, 50%), m.p. 460 C (decamp.) (Found: C, 71.2; H, 3.9; N, 25.0%; M+, 338.128 0.
C,oH14N,requires C, 71.0; H, 4.2; N, 24.8%. 12C,01H,,14N,
requires 338.128 0) ; S[dication (7) in trifluoroacetic acid]
7.6 (d, 3-H), 8.2 (d, 1-H), 8.4 (t, 2-H), 10.2 (s, b-H), and
17.2 (s, a-H).
3,lO-Di-n-buty1-3,10-dihydrotetrapyrido[2,1,6-de
2, l,6gh :2, l,6"-kl :2, 1,6-na] [1,3,5,8,10,121hexa-azacyclotetradecine (6).-The
hexa-aza-macrocycZe (4) (40 mg)
and sodium hydride (200 mg) were stirred in dioxan (10
ml) for 15 h at 20 C. n-Butyl iodide (2 ml) was added to
the mixture and was heated under reflux for 6 h, and allowed
to cool. The excess of sodium hydride was destroyed by
dropwise addition of methanol (2 ml) and the mixture was
filtered. The filtrate was evaporated to dryness and the
residue was washed with water. The yellow solid was
chromatographed on alumina whence chloroform eluted a
yellow band. The product crystallised from methanol
as pale yellow needles (22 mg, 41%), m.p. 229-231 C
(Found: C, 75.0; H, 6.7; N, 18.3. CZBH3,NB
requires C,
74.6; H , 6.7; N, 18.7%); m/e 450.254 8 (M) (12Czs1H3014N,) requires 450.253 1 ) ; G(CDC1,) 0.98 (t, CH,), 1.49
(m, NCH,CH,CH,CH,), 1.82 (m, NCH,CH2CH,CH,), 3.99
(t, NCH,CH,CH,CH,), 6.89 (cl, 3-H), 7.16 (d, 1-H), and
7.64 (t, 2-H).
We gratefully acknowledge the encouragement of Professor J. Kumanotani, in whose laboratory this work was
initiated. We also thank Mr. T. Nakayama and Mr. T.
Takeuchi for experimental assistance.
[9/1635 Received, 15th Oclnhrr, 19791

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J.C.S. Perkin I
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